Safety and Efficacy of Prolonged Use of Dalbavancin in Bone and Joint Infections.

Dalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related infection) treated with at least one dose of dalbavancin between 2016 and 2017 in 30 institutions in Spain. In order to evaluate the response, patients with or without an orthopedic implant were separated. A total of 64 patients were included. Staphylococcus epidermidis and Staphylococcus aureus were the most frequent microorganisms. The reasons for switching to dalbavancin were simplification (53.1%), adverse events (25%), or failure (21.9%). There were 7 adverse events, and no patient had to discontinue dalbavancin. In 45 cases, infection was related to an orthopedic implant. The implant material was retained in 23 cases, including that in 15 (65.2%) patients that were classified as cured and 8 (34.8%) that presented improvement. In 21 cases, the implants were removed, including those in 16 (76.2%) cases that were considered successes, 4 (19%) cases were considered improved, and 1 (4.8%) case that was considered a failure. Among the 19 cases without implants, 14 (73.7%) were considered cured, 3 (15.8%) were considered improved, and 2 (10.5%) were considered failures. The results show that dalbavancin is a well-tolerated antibiotic, even when >2 doses are administered, and is associated with a high cure rate. These are preliminary data with a short follow-up; therefore, it is necessary to gain more experience and, in the future, to establish the most appropriate dose and frequency.

Results of an early intervention programme for patients with bacteraemia: analysis of prognostic factors and mortality.

BACKGROUND: Bacteraemia is a common cause of morbidity and mortality in patients admitted to hospital. The aim of this study is to analyse the results of a two-year programme for the early optimisation of antibiotic treatment in patients admitted to the Costa del Sol Hospital (Marbella. Spain). METHODS: A prospective two-year cohort study was conducted, evaluating all episodes of bacteraemia at the Costa del Sol Hospital. Epidemiological and microbiological characteristics, any modification of the initial antibiotic treatment, prognostic risk stratification, early mortality related to the episode of bacteraemia, and mortality after the seventh day, were included in the analysis. RESULTS: Seven hundred seventy-three episodes of bacteraemia were treated, 61.6% males and 38.4% females. The mean age was 65.2 years. The condition was most commonly acquired in the community (41.4%). The bacteraemia was most frequently urological in nature (30.5%), and E coli was the microorganism most frequently isolated (31.6%). In 51.1% of the episodes, a modification was made to optimise the treatment. In the first week, 8.2% died from bacteraemia, and 4.5% had died when they were located. The highest rates of death were associated with older patients, nosocomial acquisition, no source, McCabe score rapidly fatal, Charlson index ≥3, Pitt index ≥3 and treatment remained unmodified. CONCLUSION: The existence of bacteraemia control programmes and teams composed of clinicians who are experienced in the treatment of infectious diseases, can improve the disease outcome by enabling more severe episodes of bacteraemia to be recognised and their empirical treatment optimised.

Clinical, virological and phylogenetic characterization of a multiresistant HIV-1 strain outbreak in naive patients in southern Spain.

BACKGROUND: We describe the characteristics of an HIV-1 strain with six viral reverse transcriptase mutations (D67N, T69N/D, V118I, V179D, T215S and K219Q), which we have called the Malaga strain. This strain was detected in treatment-naive patients from southern Spain. METHODS: The study was undertaken at the Virgen de la Victoria Hospital, Malaga, a reference centre for the study of HIV-1 genotype resistance in Andalusia (the 'Costa del Sol'), Spain. Genotypic resistance testing was done in an automated sequencer. Phylogenetic analysis was performed using a 630 bp region of the reverse transcriptase with the mutations mentioned. RESULTS: Between 2007 and 2014, we detected the Malaga strain in 30 treatment-naive patients. All were MSM, seen at five hospitals on the Costa del Sol. In all cases, the HIV-1 was subtype B with viral tropism R5. Phylogenetic analysis based on the reverse transcriptase sequence showed consistent grouping (with a bootstrap value of the common node of 100%) of the isolates that shared the mutation pattern mentioned. This strain has not been detected elsewhere or in previously treated patients. All of the patients treated with first-line combination ART responded. CONCLUSIONS: We report a cluster of an HIV-1 strain with multiple resistance mutations that was transmitted over a period of >8 years, affecting 30 naive patients from the same geographical area. The strain was susceptible to first-line combination ART.

The impact of an antimicrobial stewardship programme on the use of antimicrobials and the evolution of drug resistance.

Misuse of antibiotics can provoke increased bacterial resistance. There are no immediate prospects of any new broad-spectrum antibiotics, especially any with activity against enterobacteria, coming onto the market. Therefore, programmes should be implemented to optimise antimicrobial therapy. In a quasi-experimental study, the results for the pre-intervention year were compared with those for the 3 years following the application of an antimicrobial stewardship programme. We describe 862 interventions carried out as part of the stewardship programme at the Hospital Costa del Sol from 2009 to 2011. We examined the compliance of the empirical antimicrobial treatment with the programme recommendations and the treatment optimisation achieved by reducing the antibiotic spectrum and adjusting the dose, dosing interval and duration of treatment. In addition, we analysed the evolution of the sensitivity profile of the principal microorganisms and the financial savings achieved. 93 % of the treatment recommendations were accepted. The treatment actions taken were to corroborate the empirical treatment (46 % in 2009 and 31 % in 2011) and to reduce the antimicrobial spectrum taking into account the antibiogram results (37 % in 2009 and 58 % in 2011). The main drugs assessed were imipenem/meropenem, used in 38.6 % of the cases, and cefepime (20.1 %). The sensitivity profile of imipenem against Pseudomonas aeruginosa increased by 10 % in 2011. Savings in annual drug spending (direct costs) of 30,000 Euros were obtained. Stewardship programmes are useful tools for optimising antimicrobial therapy. They may contribute to preventing increased bacterial resistance and to reducing the long-term financial cost of antibiotic treatment.

Are hip hemiarthroplasty and total hip arthroplasty infections different entities? The importance of hip fractures.

Hip hemiarthroplasty (HHA) and total hip arthroplasty (THA) infections are usually considered as one entity; however, they may show important differences. We analyze these differences, as well as predictors of treatment failure (TF) and poor functional status among patients with prosthetic hip infections (PHIs). A multicenter cohort study of consecutive patients with PHIs was performed. The main outcome variable was TF after the first surgical treatment performed to treat the infection. Multivariate analysis was used to identify predictors of TF. A total of 127 patients with PHI were included (43 HHA, 84 THA). Patients with HHA infections were more frequently women (88% vs. 54%; p < 0.001), had comorbidities (86% vs. 67%, p = 0.02), and were older (median age 79 vs. 65 years, p < 0.001), and the reason for arthroplasty was more frequently a fracture (100% vs. 18%, p < 0.001). Failure of initial treatment and crude mortality were more frequent among HHA patients (44% vs. 23%, p = 0.01 and 28% vs. 7%, p = 0.001, respectively). However, HHA was not associated with TF in the multivariate analysis when hip fracture was considered; thus, variables independently associated with TF were hip fracture, inadequate surgical management, prosthesis retention, and higher C-reactive protein level. Failure of the first surgical treatment was associated with poorer functional status. HHA and THA infections showed significant differences in epidemiology, clinical features, and outcome. Although patients with HHA infections had a higher risk of TF, this was related to the reason for hip implant: a hip fracture. Success of the initial management of infection is a predictor of better clinical and functional outcome.

Differential effects of environmental enrichment and isolation housing on the hormonal and neurochemical responses to stress in the prefrontal cortex of the adult rat: relationship to working and emotional memories.

The present study was designed to investigate the modulation of the stress responses by the environmental conditions and its putative neurobiological mechanisms. For that an integrative study on the effects of environmental enrichment and isolation housing on (1) the corticosterone, dopamine and acetylcholine responses to acute restraint stress in the prefrontal cortex (PFC) of the awake rat; (2) the mRNA levels of glucocorticoid receptors (GRs) in the PFC, and (3) the behavioral responses to stress, related to the PFC (habituation to a novel environment, spatial-working memory and inhibitory avoidance response) was performed. Male Wistar rats were maintained from 3 to 6 months of age in two different conditions: enriched (EC) or impoverished (IC). Animals were stereotaxically implanted with bilateral guide cannulae in the PFC to perform microdialysis experiments to evaluate the concentrations of corticosterone, dopamine and acetylcholine. EC animals showed lower increases of corticosterone and dopamine but not of acetylcholine than IC animals in the PFC in response to acute restraint stress (20 min). In the PFC, GR mRNA levels showed a trend towards an enhancement in EC animals. EC reduced the days to learn the spatial working memory task (radial-water maze). Spatial working memory, however, was not different between groups in either basal or stress conditions. Inhibitory avoidance response was reduced in EC rats. The changes produced by EC in the neurochemical, neuroendocrine and behavioral parameters evaluated suggest that EC rats could show a better coping during an acute stress challenge.

Management of incidental durotomies in an integrated Orthopaedic and Neurosurgical Spinal Unit.

Introduction: Incidental durotomy (ID) is an intraoperative event associated to prolonged bed rest and hospital stay, antibiotic use, higher patient dissatisfaction, and leg pain among other complications of its postoperative course. Several repair techniques and postsurgical care have been proposed for its management. This study was designed to develop an agreed protocol in cases of ID among Orthopaedic Surgeons (OS) and Neurosurgeons (NS) integrated into a Spinal Surgery Unit. Research question: Incidental durotomies management protocol. Materials and methods: From 997 eligible cases operated in Hospital del Mar (Barcelona, Spain) from April 2018 to March 2022, demographic, clinical, surgical and postoperative data was collected for statistical analysis from the morbidity and mortality database, with 79 identified IDs. Redo procedures were significantly associated to OS, and cervical and anterior/lateral approaches to NS, both groups were not comparable. Results: ID occurred in 7.9% of cases, more frequently after the lockdown (p=0.03), in females (p=0.04), during posterior approaches (p=0.003), and less frequently in the cervical spine (p=0.009). IDs were linked to postoperative infections (p< 0.001) and nerve root damage (p< 0.001). Patients without ID evolved more satisfactorily during the postoperative period (p=0.002), and those with CSF leak (20/79) spent on bed rest more than twice the time as those without (p<0.001). Multivariable logistic regression showed strong association between posterior approaches and ID, between complicated postoperative courses and ID. Discussion and conclusions: ID is linked to an adverse postoperative recovery, and it should be primarily repaired under microscope, with early mobilization of patients after surgery.

Late initiation of HAART among HIV-infected patients in Spain is frequent and related to a higher rate of virological failure but not to immigrant status.

PURPOSE: To determine whether immigrant status is associated with late initiation of highly active antiretroviral treatment (HAART) and/or poor response to antiretrovirals. METHODS: GESIDA 5808 is a multicenter, retrospective cohort study (inclusion period January 2005 through December 2006) of treatment-naïve patients initiating HAART that compares HIV-infected patients who are immigrants with Spanish-born patients. A late starter (LS) was defined as any patient starting HAART with a CD4+ lymphocyte count <200 cells/µL and/or diagnosis of an AIDS-defining illness before or at the start of therapy. The primary endpoint was time to treatment failure (TTF), defined as virological failure (VF), death, opportunistic infection, treatment discontinuation/switch (D/S), or missing patient. Secondary endpoints were time to treatment failure as observed data (TTO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/S not due to VF). RESULTS: LS accounted for 56% of the patients. Lower educational and socioeconomic level and intravenous drug use (IVDU) were associated with categorization as LS, but immigrant status was not. Cox regression analysis (hazard ratio [HR]; 95% CI) between LS and non-LS patients showed no differences in TTF (0.97; 0.78-1.20) or TTO (1.18; 0.88-1.58), although it did reveal a difference in TVF (1.97; 1.18-3.29). CD4+ lymphocyte recovery was equivalent for both LS and non-LS patients (159 vs 173). CONCLUSIONS: In our cohort, immigrant status was not shown to be related to late initiation of HAART. Although LS patients did not have a longer TTF for any reason, TVF was significantly shorter. Despite universal free access to HAART in Spain, measures to ensure early diagnosis and treatment of HIV infection are necessary.

Ankle-branch index and HIV: the role of antiretrovirals.

OBJECTIVE: To study the relationship between antiretroviral (ARV) treatment and abnormal ankle-branch index (ABI) and to compare the risk factors for altered ABI. METHODS: Patients coming to the office from April 2007 until July 2007 were offered the chance to take part in the study. ABI was obtained by the standard technique. Those < or = 0.9 or > or = 1.3 were considered altered ABI. Clinical reports were reviewed to examine traditional vascular risk factors, coinfection with hepatitis C virus and/or hepatitis B virus, tobacco use, highly active antiretroviral therapy use and its components and length of use of each ARV drug. RESULTS: ABI was measured in 147 patients, 82.3% males. Thirty-three patients (22.45%) had an altered ABI, and it was related to CD4 cell nadir, dyslipidaemia and protease inhibitor (PI) use. When logistic regression was carried out, only dyslipidaemia (OR 2.68, CI 95%: 1.06-6.91) and PI use (OR 2.79, CI 95%: 1.15-6.54) remained in the model. CONCLUSIONS: Altered ABI is associated with PI use independently of dyslipidaemia. Probably, it marks patients with high vascular risk not identified with traditional scales.

Effectiveness and safety of simplification from tenofovir-lamivudine (TDF-3TC) to tenofovir-emtricitabine (TDF-FTC) co-formulation (Truvada) in virologically suppressed HIV-infected patients on HAART.

The objective was to evaluate the effectiveness and safety of simplification from tenofovir-lamivudine (TDF-3TC) to Truvada (TVD) in virologically suppressed HIV patients. We carried out an open-label, multicentre, non-controlled study of HIV patients on a stable regimen including TDF-3TC who switched from TDF-3TC to TVD. Viral load responses at 24 and 48 weeks were evaluated. Changes in the calculated glomerular filtration rates (cGFR; Cockcroft-Gault equation) were analysed at baseline and at 24 and 48 weeks. Patients with drug-related nephrotoxicity (cGFR < 60 mL/min at 48 weeks or interruption of TVD because of renal toxicity) were analysed in detail. Two hundred and ninety-five patients with a mean time on TDF-3TC of 19.9 months (range 8.8-29.8) were enrolled. The third drug was a non-nucleoside reverse transcriptase inhibitor, which was administered to 187 patients (76.4% efavirenz) and a protease inhibitor was administered to 108 (43.5% lopinavir/ritonavir). At 48 weeks, 85.7% of the patients were still taking the same regimen, all with an undetectable viral load. The cGFR (mL/min) decreased from baseline (111 [89-130]) to 48 weeks (105 [84-121]); p < 0.0001. The percentage of patients with a cGFR <60 mL/min at 48 weeks was 3.5. Six patients ceased TVD because of drug-related nephrotoxicity. The only factors associated with nephrotoxicity were age, baseline weight and cGFR. Simplification from TDF-3TC to TVD was associated with a decrease in cGFR, with a low prevalence of nephrotoxicity at 48 weeks.

Do magnetic phosphorus adsorbents used for lake restoration impact on zooplankton community?

Magnetic microparticles (MPs) have been recently proposed as innovative and promising dissolved inorganic phosphorus (DIP) adsorbents. However, before using them in a whole-lake restoration project, it is essential to assess their toxicological effects (direct and indirect) on aquatic biota. In the present study we hypothesized that zooplankton community is affected by MPs used for lake restoration. To test our hypothesis we designed a microcosms experiment (n = 15) containing lake water and surface sediment from a hypertrophic lake. Temporal changes (70 days) on physico-chemical conditions and on zooplankton structure (rotifers, copepods and branchiopods) were monitored under different scenarios. In particular, three different treatments were considered: no addition of MPs (control) and MPs addition (1.4 g MPs L-1) on the surface water layer (T-W) and on the sediment (T-S). After 24 h of contact time, MPs were removed with a magnetic rake. A total of 15 zooplankton species (12 rotifers, 1 branchiopod and 2 copepods) were recorded and a high abundance of zooplankton was registered during the experiment for all treatments. No significant differences (RM-ANOVA test; p > 0.05) in total abundance, species richness and species diversity among treatments were found. The absence of any effect of MPs on zooplankton can be explained because MPs did not significantly alter any of its physico-chemical (e.g. temperature, pH, O2) or biological (e.g. food quantity and quality) drivers. These results confirm the suitability of MPs as a promising tool for removing DIP in eutrophic aquatic ecosystems.

Very low prevalence and no clinical significance of occult hepatitis B in a cohort of HIV-infected patients with isolated anti-HBc seropositivity: the BHOI study.

PURPOSE: Data on occult HBV infection in HIV patients are conflicting. We aimed to analyse the prevalence and clinical significance of occult hepatitis B in HIV-infected subjects. METHOD: An open-label, cross-sectional, multicentre study including all subjects with isolated anti-HBc seropositivity from a cohort of 3,030 HIV-infected patients was undertaken. HBsAg and HBsAb were both negative in all cases, and those patients with acute or convalescent hepatitis B were excluded. HBV DNA was quantified by PCR with a detection limit of 20 IU/mL. RESULTS: We found 5 cases (2.5%) of occult hepatitis B among 202 HIV-patients with isolated anti-HBc. The mean HBV DNA was 66 (15-112) IU/mL, none had symptomatic hepatitis, and their features, including aminotransferase levels, were similar to those without occult HBV infection. CONCLUSIONS: Occult hepatitis due to HBV is very unusual in HIV-positive patients with isolated anti-HBc. The use of standard regimens of HAART including drugs with activity against HBV might underestimate the prevalence of occult HBV infection. These patients had a very low viral load, no identifiable risk factors, and no greater risk of hypertransaminasaemia or the development of symptomatic hepatitis.

A microcosm experiment to determine the consequences of magnetic microparticles application on water quality and sediment phosphorus pools.

This study used microcosms to evaluate the effects of adding iron (Fe) magnetic microparticles (MPs) on water quality, focusing on P concentrations in the water column and sediment. Two treatments were considered for a constant 85:1 MP:PMobile molar ratio: T-W, applying MPs on the surface water layer; and T-S, applying MPs on the sediment. MP addition reduced P concentrations in lake water and sediment, with both treatments producing a mean reduction of 68±6% in dissolved inorganic P concentration (DIP) over a 70-day oxic period and reductions of 80±8% (T-W) and 80±4% (T-S) over a 5-day anoxic period. MPs also decreased reactive silicate (Si) concentrations by around 50% in both periods, but dissolved organic carbon (DOC) was reduced by only 15% at 24h after MP addition. Despite the marked decrease in DIP concentration due to MP addition, there was no reduction in chlorophyll a (Chla), because post-treatment total P concentrations (>200µgL-1vs. >700µgL-1 before treatments) remained higher than required for changes in the biological community (0.05-0.1mgL-1). With T-S treatment, there was a reduction of 15% in P bound to Al oxides, clay minerals, and humic substances (P→NaOH) and of 12% in labile organic P (Org-PLabile) versus controls. P bound to humic substances (P→NaOH, Humic) was reduced by 11-22% in both treatments. Finally, T-W rather than T-S treatments are recommended for future whole-lake applications to achieve more effective P removal from water and sediment and a higher percentage MP recovery.

Subcellular fractions of Brucella ovis distinctively induce the production of interleukin-2, interleukin-4, and interferon-gamma in mice.

The aim of this study was to evaluate the effect of 3 Brucella ovis subcellular protein fractions: Outer membrane (OMP), inner membrane (IMP), and cytoplasm (CP), on cellular immune response by in vitro production of interleukin (IL)-2, IL-4, and interferon (IFN)-gamma. Each fraction was inoculated 3 times into Balb/c mice, primary cultures of mice spleen cells were done, and these were then stimulated with the fractions. Culture supernatants were collected at 24, 48, 72, 96, and 120 h postinoculation. Cytokine concentration was measured by Duoset-enzyme-linked immunosorbent assay (ELISA). The OMP fraction induced highest cellular immune response of 1000 pg/mL of IL-2 at 24 h, which decreased to < 100 pg/mL by 96 h. The IL-2 response for the IMP fraction was low at 24 h, but exceeded that of the OMP fraction at 72, 96, and 120 h. The CP showed a poor IL response. Regarding the IFN-gamma production, OMP and IMP induced a high response at 120 h. These results open the possibility for the use of B. ovis outer and inner membrane proteins as a subcellular vaccine.

Alternative splicing generates a novel non-secretable resistin isoform in Wistar rats.

Resistin is a secreted adipose tissue hormone that belongs to the resistin-like molecule family. We report here a new alternatively spliced isoform of the rat resistin gene, named S-resistin (short resistin), detected in adipose tissue by reverse transcription-polymerase chain reaction (RT-PCR). A comparison of this cDNA variant and genomic sequences indicates the lack of the second exon containing the secretory consensus signal. Both cDNAs, resistin and S-resistin, were carboxy-tagged with FLAG epitope and transiently expressed in cultured cell lines. While the resistin-FLAG construct gives the expected pattern for a secretion protein, the S-resistin-FLAG construct yielded a predominant nuclear staining. These results indicate that this splicing event regulates the fate and probably the function of the mature protein.

Glutamatergic neurotransmission in aging: a critical perspective.

The effects of aging on glutamate neurotransmission in the brain is reviewed and evaluated. Glutamate is the neurotransmitter in most of the excitatory synapses and appears to be involved in functions such as motor behaviour, cognition and emotion, which alter with age. However, relatively few studies have been conducted to study the relationship between glutamate and aging of the brain. The studies presented here indicate the existence of a number of changes in the glutamatergic system during the normal process of aging. First, an age-related decrease of glutamate content in tissue from cerebral cortex and hippocampus has been reported, although it may be mainly a consequence of changes in metabolic activity rather than glutamatergic neurotransmission. On the other hand, studies in vitro and in vivo have shown no changes in glutamate release during aging. Since glutamate sampled in most of these studies is the result of a balance between release and uptake processes, the lack of changes in glutamate release may be due to compensatory changes in glutamate uptake. In fact, a reduced glutamate uptake capacity, as well as a loss in the number of high affinity glutamate transporters in glutamatergic terminals of aged rats, have been described. However, the most significant and consistent finding is the decrease in the density of glutamatergic NMDA receptors with age. A new perspective, in which glutamate interacts with other neurotransmitters to conform the substrates of specific circuits of the brain and its relevance to aging, is included in this review. In particular, studies from our laboratory suggest the existence of age-related changes in the interaction between glutamate and other neurotransmitters, e.g. dopamine and GABA, which are regionally specific.

Endogenous glutamate-taurine interaction in striatum and nucleus accumbens of the freely moving rat: studies during the normal process of aging.

Using microdialysis, the effects of endogenous glutamate on extracellular concentrations of taurine, in striatum and nucleus accumbens of the awake rat during the normal process of aging were investigated. The glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was perfused through the microdialysis probe to increase the endogenous concentration of glutamate. Young (2-4 months), middle aged (12-14 months), aged (27-32 months) and very aged (37 months) male Wistar rats were used. PDC (1, 2 and 4 mM) produced a dose-related increase of extracellular concentrations of glutamate and taurine in striatum and nucleus accumbens in all groups of age. Increases of glutamate, but not of taurine, decreased during aging in striatum. In nucleus accumbens there were no age-related changes in the increases of glutamate and taurine induced by PDC. In all age groups, increases of extracellular taurine were significantly correlated with increases of extracellular glutamate. However, when these taurine-glutamate correlations for all groups of age were compared, no statistical differences were found. These results show first that a decrease in the increases of glutamate produced by the glutamate reuptake inhibitor in striatum, but not in nucleus accumbens, is produced by age; second that glutamate-taurine interaction in striatum and nucleus accumbens does not change during the normal process of aging.

Amphetamine releases GABA in striatum of the freely moving rat: involvement of calcium and high affinity transporter mechanisms.

Using microdialysis the effect was investigated of amphetamine (AMPH) infusions into the striatum on the release of GABA in the freely moving rat. AMPH (5, 10 and 20 microg/microl), infused through a microdialysis probe at the rate of 2.5 microl/min, produced a dose-related increase in extracellular concentrations of GABA. At the highest dose (20 microg/microl), AMPH increased GABA from 0.08 +/- 0.01 to 0.67 +/- 0.14 microM. Increases in extracellular GABA produced by AMPH were both calcium-dependent and high affinity GABA transporter-mediated. A medium free of calcium reduced the increase of extracellular GABA produced by AMPH by 37%. Nipecotic acid (2, 4 and 8 mM), a specific GABA re-uptake blocker, significantly attenuated increases in extracellular GABA, but not GLU, produced by AMPH (20 microg/microl). This study is the first in vivo evidence showing the release of GABA produced by AMPH through a high affinity transporter mechanism.